Abstract

Background

Obesity plays an important role in the pathogenesis of hypertension. Renal dopamine
D1-like receptor-mediated diuresis and natriuresis are impaired in the obese Zucker
rat, an obesity-related hypertensive rat model. The role of arterial D1 receptors in the hypertension of obese Zucker rats is not clear.

Methods

Plasma glucose and insulin concentrations and blood pressure were measured. The vasodilatory
response of isolated mesenteric arteries was evaluated using a small vessel myograph.
The expression and phosphorylation of D1 receptors were quantified by co-immunoprecipitation and immunoblotting To determine
the effect of hyperinsulinemia and hyperglycemia on the function of the arterial D1 receptor, we studied obese Zucker rats (six to eight-weeks old) fed (6 weeks) vehicle
or rosiglitazone, an insulin sensitizer (10 mg/kg per day) and lean Zucker rats (eight
to ten-weeks old), fed high-fat diet to induce hyperinsulinemia or injected intraperitoneally
with streptomycin (STZ) to induce hyperglycemia.

Results

In obese Zucker rats, the vasorelaxant effect of D1-like receptors was impaired that could be ascribed to decreased arterial D1 receptor expression and increased D1 receptor phosphorylation. In these obese rats, rosiglitazone normalized the arterial
D1 receptor expression and phosphorylation and improved the D1-like receptor-mediated vasorelaxation. We also found that D1 receptor-dependent vasorelaxation was decreased in lean Zucker rats with hyperinsulinemia
or hyperglycemia but the D1 receptor dysfunction was greater in the former than in the latter group. The ability
of insulin and glucose to decrease D1 receptor expression and increase its phosphorylation were confirmed in studies of
rat aortic smooth muscle cells.